During the past 10 years. Pilot Feasibility Project Applications have been solicited on an annual basis by a Yale University School of Medicine wide call for applications to all faculty members. Since 1999, this announcement has been included on the Center's website as well as distributed by e-mail to all medical school and basic science faculty. The primary purpose of the pilot grants is to obtain data to enable applications for future R01 funding. Candidates for funding in order of priority consist of: 1) Senior post-doctoral fellows and junior faculty without liver related research support 2) Established investigators in other fields and 3) Center members who are changing directions of their research. Existing Center members are eligible for pilot funding only if they request support for funding of new departures not previously supported or construed as a continuation of their present research base. No applicant receives funding for more than one project and no more than 1-2 years in a given 5-year grant award period. Only 3 investigators received a 2nd year of pilot funding during the past 5 years, and budgets were reduced for 2 of them in the second year. Three years of funding was provided to the Named New Investigator (Iwakiri) per Center guidelines. Thus, the vast majority of the pilots were funded for only one year. The call for applications for funding is made in Dec-Jan of each year; Letters of intent to submit an application for pilot-feasibility funding are submitted to the Center Administrators by February 1st and the Director and Executive Committee then establish whether the applicant is eligible for pilot funding. Applications are denied if they do not fill the above-mentioned criteria or are not focused on the Center's mission. Applications from approved applicants are received in March following strict guidelines for page limits and using a PHS 398 grant format. These guidelines are distributed to all applicants for pilot funding and are posted on the Center's web site. The applications are reviewed briefly for compliance by the Executive committee and assigned to two primary reviewers primarily inside the University but outside the institution as expertise demands. Following receipt of the reviews, the Executive Committee either approves or rejects the applications and letters of decision are sent by the Center Director to each applicant with edited reviews. If the proposal is approved, it is returned to the applicant for suggested improvements and budget alterations. A final revised application is received by early May. All of these applications are then forwarded to the External Advisory Board together with assignments of primary and secondary reviewers. The External Advisory Board subsequently meets at the Center as a study section in late May or early June. Presentations are heard from the pilot applicants and independently votes approval or disapproval and establishes a priority score and suggested budget. This process then determines the funding of the Pilot Feasibility Program for the next fiscal year that begins September 1st. The Center Director then communicates these findings in a letter to the applicants. The only exception to this procedure is the year of the competitive renewal when, due to time constraints to the application deadline, the External Advisory Board reviews the pilot applications via email and holds a conference call if needed to assign final priorities for funding. Annual reports for completed pilot projects or applications for a second year of funding are also reviewed at the time of the External Advisory Board Meeting. A 2nd year of funding is not automatic and is approved only if there is significant progress during the first year of the award and only if the relative scientific merit is greater than other competing projects which are under current review. In addition to their presentations at the annual External Advisory Board meeting, Pilots recipients often participate as part of the Center's Enrichment Program in the weekly seminar series and the biannual Center retreats. Pilots are terminated if the investigator leaves the institution or otherwise does not carry out the original intent of the project. Requests for carryover funding to the next year must be approved by the Executive Committee and are allowed only in exceptional circumstances.